The evolution and spread of antibiotic resistance among bacteria is a major public health problem today, especially in the hospital setting with the emergence of multidrug resistant strains. Intensive research efforts have led to the development of new antibiotics effective against these resistant strains. Nevertheless, through use, mechanisms of resistance to these drugs emerge and limit their efficacy.
In view of this phenomenon, antimicrobial peptides (AMP) appear very promising for the design of new therapeutic agents. Cationic antimicrobial peptides are thought to be one of the key components of the innate immune system of pluricellular organisms which provides first-line defence against pathogens. The interest of these peptides lies on the one hand in their very broad spectrum of activity enabling in particular their use in the treatment of infections caused by multidrug resistant strains. Secondly, their mode of action is based on permeabilisation or rapid fragmentation of the microorganism membrane and is therefore unlikely to lead to the development of resistance mechanisms.
Antimicrobial peptides have been identified in plants, insects, amphibia and mammals. Amphibian skin represents a major source of antimicrobial peptides and every species of frog possesses its specific peptide repertoire generally composed of 10 to 15 AMP.
Frogs of the Ranidae family are very numerous and this family currently counts 16 genera and 338 species. These frogs synthesize and secrete a remarkable diversity of AMP which have been classified into 13 families (Conlon et al., 2008 and 2009). One such family, the temporins, comprises AMP of small size (generally between 10 and 14 residues) the sequences of which vary widely according to species. More than 60 members of the temporin family have been identified. These temporins have been isolated from several Rana species such as for example Rana temporaria (Simmaco et al., 1996), Rana esculenta (Simmaco et al., 1990), Rana japonica (Isaacson et al., 2002), Rana ornativentris (Kim et al., 2001) and Pelophylax (Rana) saharica (Abbassi et al., 2008).
Unlike the other 12 families of Ranidae peptides, the temporins lack the “Rana box” motif, a C-terminal heptapeptide domain cyclised by a disulphide bridge (Mangoni, 2006). Furthermore, the majority of temporins contain a single basic residue which confers a net charge of +2 at physiological pH.
Generally, the temporins are particularly active against Gram-positive bacteria and yeasts but they also exhibit antifungal properties (Rollins-Smith et al., 2003) and, for some, antiviral properties (Chinchar et al., 2004).
Recent studies on temporins A, B (Mangoni et al., 2006) and SHa (Abbassi et al., 2008) revealed that these peptides exhibit antiparasitic activity against protozoa belonging to the genus Leishmania, which are the causal agents of leishmaniasis. Apart from these temporins, very few AMP display antiparasitic activity: dermaseptins and polypeptide YY (also isolated from frog skin); indolicidin (isolated from bovine neutrophil granules); gomesin (isolated from the spider Acanthoscurria gomesiana); cecropin-melittin hybrids (obtained from insect molecules).
Leishmaniasis is an extremely widespread disease found across much of the world, essentially in India, South America, Africa and the Mediterranean basin. The parasite infects several million individuals every year. Depending on the Leishmania species, leishmaniasis can be of the cutaneous, mucocutaneous or visceral form. For example, visceral leishmaniasis, the most serious form and potentially fatal if untreated, is caused by two Leishmania species: Leishmania infantum and Leishmania donovani. The Leishmania life cycle comprises two successive morphological stages: the promastigote stage (free form in the gut of the insect vector, the sandfly) and the amastigote stage (intracellular form infecting the mononuclear phagocytes of the mammalian host).
The first-line therapy of leishmaniasis consists in the use of antimonials such as meglumine antimionate (Glucantime®) or soduim stibogluconate (Pentostam®). However, the efficacy of antimony is eroding due to the emergence of high level resistance which can reach 60% according to geographical location. Despite the availability of alternative treatments such as amphotericin B (Ambisome®) and miltefosin (Impavido®), there is an urgent need to find new drugs to fight this disease.